Endocrinology and Metabolism

Editorial

Thyroid Thyroid Cancer Screening
To Screen or Not to Screen?: Do Joon Park; Endocrinol Metab. 2023;38(1):69-71. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.104

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Original Articles

Thyroid
Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves’ Disease: Min Joo Kim, Sun Wook Cho, Ye An Kim, Hoon Sung Choi, Young Joo Park, Do Joon Park, Bo Youn Cho; Endocrinol Metab. 2022;37(3):524-532. Published online June 16, 2022; DOI: https://doi.org/10.3803/EnM.2022.1418

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Background
Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease.
Methods
Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy.
Results
The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months.
Conclusion
Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Citations

Citations to this article as recorded by

The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease
Jin Yu, Han-Sang Baek, Chaiho Jeong, Kwanhoon Jo, Jeongmin Lee, Jeonghoon Ha, Min Hee Kim, Jungmin Lee, Dong-Jun Lim
Endocrinology and Metabolism.2023; 38(3): 338. CrossRef
Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves’ disease
Yuyang Ze, Fei Shao, Xuefeng Feng, Shanmei Shen, Yan Bi, Dalong Zhu, Xiaowen Zhang
BMC Endocrine Disorders.2022;[Epub] CrossRef

Calcium & Bone Metabolism
Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study: Ye An Kim, Ji Won Yoon, Young Lee, Hyuk Jin Choi, Jae Won Yun, Eunsin Bae, Seung-Hyun Kwon, So Eun Ahn, Ah-Ra Do, Heejin Jin, Sungho Won, Do Joon Park, Chan Soo Shin, Je Hyun Seo; Endocrinol Metab. 2021;36(6):1189-1200. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1241

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Background
Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).
Methods
We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.
Results
rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.
Conclusion
The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Citations

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Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization
Caroline De Souza Silverio , Carolina Bonilla
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Critical Reviews in Food Science and Nutrition.2023; : 1. CrossRef
Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study
Ji Hyun Lee, Ye An Kim, Young Sik Kim, Young Lee, Je Hyun Seo
Nutrients.2023; 15(13): 3043. CrossRef
Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait
Abdur Rahman, Mohamed Abu-Farha, Arshad Channanath, Maha M. Hammad, Emil Anoop, Betty Chandy, Motasem Melhem, Fahd Al-Mulla, Thangavel Alphonse Thanaraj, Jehad Abubaker
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Rihwa Choi, Sung-Eun Cho, Sang Gon Lee, Eun Hee Lee
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The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies
Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, Monica Montopoli
Antioxidants.2022; 11(6): 1090. CrossRef
A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts
Young Lee, Ji Won Yoon, Ye An Kim, Hyuk Jin Choi, Byung Woo Yoon, Je Hyun Seo
Genes.2022; 13(9): 1553. CrossRef
Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health
Elina Hyppönen, Karani S. Vimaleswaran, Ang Zhou
Nutrients.2022; 14(20): 4408. CrossRef
On the Centennial of Vitamin D—Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications
Leonidas H. Duntas, Krystallenia I. Alexandraki
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The genetic and epigenetic contributions to the development of nutritional rickets
Innocent Ogunmwonyi, Adewale Adebajo, Jeremy Mark Wilkinson
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Thyroid
Comparison of Korean vs. American Thyroid Imaging Reporting and Data System in Malignancy Risk Assessment of Indeterminate Thyroid Nodules: Sunyoung Kang, Seul Ki Kwon, Hoon Sung Choi, Min Joo Kim, Young Joo Park, Do Joon Park, Sun Wook Cho; Endocrinol Metab. 2021;36(5):1111-1120. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1208

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Background
The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules.
Methods
Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled.
Results
Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change.
Conclusion
K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.

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Is the nodule location a predictive risk factor for cancer in AUS/FLUS thyroid nodules? A retrospective cohort study
Saad M. Alqahtani, Bassam A. Altalhi, Yousef S. Alalawi, Saif S. Al-Sobhi
Asian Journal of Surgery.2024;[Epub] CrossRef
Diagnostic Performance of Various Ultrasound Risk Stratification Systems for Benign and Malignant Thyroid Nodules: A Meta-Analysis
Ji-Sun Kim, Byung Guk Kim, Gulnaz Stybayeva, Se Hwan Hwang
Cancers.2023; 15(2): 424. CrossRef
The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules
Saad M. Alqahtani, Saif S. Al-Sobhi, Mohammed A. Alturiqy, Riyadh I. Alsalloum, Hindi N. Al-Hindi
Journal of Taibah University Medical Sciences.2023; 18(3): 506. CrossRef
Diagnostic Performance of Six Ultrasound Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Network Meta-Analysis
Do Hyun Kim, Sung Won Kim, Mohammed Abdullah Basurrah, Jueun Lee, Se Hwan Hwang
American Journal of Roentgenology.2023; 220(6): 791. CrossRef
Diagnostic efficiency among Eu-/C-/ACR-TIRADS and S-Detect for thyroid nodules: a systematic review and network meta-analysis
Longtao Yang, Cong Li, Zhe Chen, Shaqi He, Zhiyuan Wang, Jun Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Comparison of diagnostic performance of two ultrasound risk stratification systems for thyroid nodules: a systematic review and meta-analysis
Yun Jin Kang, Hee Sun Ahn, Gulnaz Stybayeva, Ju Eun Lee, Se Hwan Hwang
La radiologia medica.2023; 128(11): 1407. CrossRef
Diagnostic Performance of ACR and Kwak TI-RADS for Benign and Malignant Thyroid Nodules: An Update Systematic Review and Meta-Analysis
Yun Jin Kang, Gulnaz Stybayeya, Ju Eun Lee, Se Hwan Hwang
Cancers.2022; 14(23): 5961. CrossRef
Comparison of Thyroid Imaging Reporting and Data Systems in Malignancy Risk Stratification of Indeterminate Thyroid Nodules
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Clinical Study
A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol: Eun Kyung Lee, You Jin Lee, Young Joo Park, Jae Hoon Moon, Ka Hee Yi, Koon Soon Kim, Joo Hee Lee, Sun Wook Cho, Jungnam Joo, Yul Hwangbo, Sujeong Go, Do Joon Park; Endocrinol Metab. 2020;35(3):571-577. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.681

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Abstract PDF Supplementary Material PubReader ePub: Background
Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades.
Methods
This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio <0.4). Patients choose to undergo RAI ablation (¹³¹I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (¹³¹I or ¹²³I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL.
Conclusion
This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.

Clinical Study
Postoperative Thyroid-Stimulating Hormone Levels Did Not Affect Recurrence after Thyroid Lobectomy in Patients with Papillary Thyroid Cancer: Myung-Chul Lee, Min Joo Kim, Hoon Sung Choi, Sun Wook Cho, Guk Haeng Lee, Young Joo Park, Do Joon Park; Endocrinol Metab. 2019;34(2):150-157. Published online May 10, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.150

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Background

Thyroid-stimulating hormone (TSH) suppression is recommended for patients who undergo thyroidectomy for differentiated thyroid cancer (DTC). However, the impact of TSH suppression on clinical outcomes in low-risk DTC remains uncertain. Therefore, we investigated the effects of postoperative TSH levels on recurrence in patients with low-risk DTC after thyroid lobectomy.

Methods

Patients (n=1,528) who underwent thyroid lobectomy for papillary thyroid carcinoma between 2000 and 2012 were included in this study. According to the mean and dominant TSH values during the entire follow-up period or 5 years, patients were divided into four groups (<0.5, 0.5 to 1.9, 2.0 to 4.4, and ≥4.5 mIU/L). Recurrence-free survival was compared among the groups.

Results

During the 5.6 years of follow-up, 21 patients (1.4%) experienced recurrence. Mean TSH levels were within the recommended low-normal range (0.5 to 1.9 mIU/L) during the total follow-up period or 5 years in 38.1% or 36.0% of patients. The mean and dominant TSH values did not affect recurrence-free survival. Adjustment for other risk factors did not alter the results.

Conclusion

Serum TSH levels did not affect short-term recurrence in patients with low-risk DTC after thyroid lobectomy. TSH suppression should be conducted more selectively.

Citations

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Corrigendum

Miscellaneous
Corrigendum: Author's Name Correction. Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro): Jae Hoon Moon, Ji-hoon Kim, Eun Kyung Lee, Kyu Eun Lee, Sung Hye Kong, Yeo Koon Kim, Woo-Jin Jeong, Chang Yoon Lee, Roh-Eul Yoo, Yul Hwangbo, Young Shin Song, Min Joo Kim, Sun Wook Cho, Su-jin Kim, Eun-Jae Chung, June Young Choi, Chang Hwan Ryu, You Jin Lee, Jeong Hun Hah, Yuh-Seog Jung, Junsun Ryu, Yunji Hwang, Sue K. Park, Ho Kyung Sung, Ka Hee Yi, Do Joon Park, Young Joo Park; Endocrinol Metab. 2018;33(3):427. Published online August 14, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.427

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Invasiveness and Metastatic Aggressiveness in Small Differentiated Thyroid Cancers: Demography of Small Papillary Thyroid Carcinomas in the Swedish Population
Haytham Bayadsi, Martin Bergman, Malin Sund, Joakim Hennings
World Journal of Surgery.2020; 44(2): 461. CrossRef
Clinical and pathologic predictors of lymph node metastasis in papillary thyroid microcarcinomas
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Original Articles

Thyroid
Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro): Jae Hoon Moon, Ji-hoon Kim, Eun Kyung Lee, Kyu Eun Lee, Sung Hye Kong, Yeo Koon Kim, Woo-jin Jung, Chang Yoon Lee, Roh-Eul Yoo, Yul Hwangbo, Young Shin Song, Min Joo Kim, Sun Wook Cho, Su-jin Kim, Eun Jae Jung, June Young Choi, Chang Hwan Ryu, You Jin Lee, Jeong Hun Hah, Yuh-Seog Jung, Junsun Ryu, Yunji Hwang, Sue K. Park, Ho Kyung Sung, Ka Hee Yi, Do Joon Park, Young Joo Park; Endocrinol Metab. 2018;33(2):278-286. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.278

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Background

The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups.

Methods

This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis.

Results

Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014).

Conclusion

The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

Citations

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2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules
Eun Kyung Lee, Young Joo Park
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Psychological adjustment to initial treatment for low‐risk thyroid cancer: Preliminary study
Gabriella T. Seo, Mark L. Urken, Lauren E. Wein, Michael P. Saturno, Danielle Kapustin, Monica H. Xing, Lauren E. Yue, Eric M. Dowling, Tracey A. Revenson, Katherine J. Roberts, Robert Michael Tuttle
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Response to Letter to the Editor on Surgical Outcomes in Patients With Low-Risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation Following Active Surveillance: A Multicenter Prospective Cohort Study
Hyeonuk Hwang, June Young Choi, Jae Hoon Moon, Eun Kyung Lee, Young Joo Park, Su-jin Kim, Yuh-Seog Jung
Annals of Surgery Open.2023; 4(3): e311. CrossRef
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Claudio R. Cernea, Leandro Luongo Matos, Cecília Eugênio, Giovanna Mattos Ferreira, Yasmin Sa Cerqueira, Ana Kober N. Leite, Felipe A. B. Vanderlei, Dorival de Carlucci, Renato N. Gotoda, Flávio C. Hojaij, Vergilius J. F. Araújo-Filho
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Active Surveillance Versus Thyroid Surgery for Differentiated Thyroid Cancer: A Systematic Review
Roger Chou, Tracy Dana, Megan Haymart, Angela M. Leung, Ralph P. Tufano, Julie Ann Sosa, Matthew D. Ringel
Thyroid.2022; 32(4): 351. CrossRef
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Active Surveillance Versus Immediate Surgery for Low-Risk Papillary Thyroid Microcarcinoma Patients in South Korea: A Cost-Minimization Analysis from the MAeSTro Study
Kyungsik Kim, June Young Choi, Su-jin Kim, Eun Kyung Lee, Young Ki Lee, Jun Sun Ryu, Kyu Eun Lee, Jae Hoon Moon, Young Joo Park, Sun Wook Cho, Sue K. Park
Thyroid.2022; 32(6): 648. CrossRef
A cross-sectional survey of patient treatment choice in a multicenter prospective cohort study on active surveillance of papillary thyroid microcarcinoma (MAeSTro)
Yul Hwangbo, June Young Choi, Eun Kyung Lee, Chang Hwan Ryu, Sun Wook Cho, Eun Jae Chung, Jeong Hun Hah, Woo-Jin Jeong, Sue K. Park, Yuh-Seog Jung, Ji-hoon Kim, Min Joo Kim, Su-jin Kim, Yeo Koon Kim, Chang Yoon Lee, Ji Ye Lee, You Jin Lee, Hyeong Won Yu,
Thyroid.2022;[Epub] CrossRef
Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea
Eun Kyung Lee, Jae Hoon Moon, Yul Hwangbo, Chang Hwan Ryu, Sun Wook Cho, June Young Choi, Eun-Jae Chung, Woo-Jin Jeong, Yuh-Seog Jung, Junsun Ryu, Su-jin Kim, Min Joo Kim, Yeo Koon Kim, Chang Yoon Lee, Ji Ye Lee, Hyeong Won Yu, Jeong Hun Hah, Kyu Eun Lee,
Thyroid.2022; 32(11): 1328. CrossRef
Indications and Strategy for Active Surveillance of Adult Low-Risk Papillary Thyroid Microcarcinoma: Consensus Statements from the Japan Association of Endocrine Surgery Task Force on Management for Papillary Thyroid Microcarcinoma
Iwao Sugitani, Yasuhiro Ito, Dai Takeuchi, Hirotaka Nakayama, Chie Masaki, Hisakazu Shindo, Masanori Teshima, Kazuhiko Horiguchi, Yusaku Yoshida, Toshiharu Kanai, Mitsuyoshi Hirokawa, Kiyomi Y. Hames, Isao Tabei, Akira Miyauchi
Thyroid.2021; 31(2): 183. CrossRef
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Jae Hoon Moon, Chang Hwan Ryu, Sun Wook Cho, June Young Choi, Eun-Jae Chung, Jeong Hun Hah, Yul Hwangbo, Woo-Jin Jeong, Yuh-Seog Jung, Ji-hoon Kim, Min Joo Kim, Su-jin Kim, Yeo Koon Kim, Chang Yoon Lee, Eun Kyung Lee, Ji Ye Lee, Kyu Eun Lee, You Jin Lee,
The Journal of Clinical Endocrinology & Metabolism.2021; 106(3): 724. CrossRef
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Susan C Pitt, Nan Yang, Megan C Saucke, Nicholas Marka, Bret Hanlon, Kristin L Long, Alexandria D McDow, J P Brito, Benjamin R Roman
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Ryuta Nagaoka, Aya Ebina, Kazuhisa Toda, Tomoo Jikuzono, Marie Saitou, Masaomi Sen, Hiroko Kazusaka, Mami Matsui, Keiko Yamada, Hiroki Mitani, Iwao Sugitani
World Journal of Surgery.2021; 45(9): 2769. CrossRef
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Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinology and Metabolism.2021; 36(4): 717. CrossRef
The Concept of Economic Evaluation and Its Application in Thyroid Cancer Research
Kyungsik Kim, Mijin Kim, Woojin Lim, Bo Hyun Kim, Sue K. Park
Endocrinology and Metabolism.2021; 36(4): 725. CrossRef
Genomic and Transcriptomic Characteristics According to Size of Papillary Thyroid Microcarcinoma
Young Shin Song, Byung-Hee Kang, Seungbok Lee, Seong-Keun Yoo, Young Sik Choi, Jungsun Park, Dong Yoon Park, Kyu Eun Lee, Jeong-Sun Seo, Young Joo Park
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Alvaro Sanabria
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Alexandra Koshkina, Rouhi Fazelzad, Iwao Sugitani, Akira Miyauchi, Lehana Thabane, David P. Goldstein, Sangeet Ghai, Anna M. Sawka
JAMA Otolaryngology–Head & Neck Surgery.2020; 146(6): 552. CrossRef
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Fabian Pitoia, Anabella Smulever
World Journal of Clinical Oncology.2020; 11(6): 320. CrossRef
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Jolanta Krajewska, Aleksandra Kukulska, Malgorzata Oczko-Wojciechowska, Agnieszka Kotecka-Blicharz, Katarzyna Drosik-Rutowicz, Malgorzata Haras-Gil, Barbara Jarzab, Daria Handkiewicz-Junak
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Endocrinología, Diabetes y Nutrición.2019; 66(8): 469. CrossRef
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Juan C Galofré
Endocrinología, Diabetes y Nutrición (English ed.).2019; 66(8): 469. CrossRef
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Allen S. Ho, Irene Chen, Michelle Melany, Wendy L. Sacks
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Thyroid
Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq: Sung Hye Kong, Jung Ah Lim, Young Shin Song, Shinje Moon, Ye An Kim, Min Joo Kim, Sun Wook Cho, Jae Hoon Moon, Ka Hee Yi, Do Joon Park, Bo Youn Cho, Young Joo Park; Endocrinol Metab. 2018;33(2):228-235. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.228

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Background

After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of ¹³¹I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.

Methods

Total 636 patients who received ¹³¹I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.

Results

In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.

Conclusion

Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

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Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients
Liu Xiao, Wen Jie Zhang, Yue Qi Wang, Lin Li
Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2021; 40(1): 30. CrossRef
Valores pronósticos de la captación en estrella de 131I en pacientes con cáncer diferenciado de tiroides
L. Xiao, W.J. Zhang, Y.Q. Wang, L. Li
Revista Española de Medicina Nuclear e Imagen Molecular.2021; 40(1): 30. CrossRef
Comparison between planar and single-photon computed tomography images for radiation intensity quantification in iodine-131 scintigraphy
Yusuke Iizuka, Tomohiro Katagiri, Minoru Inoue, Kiyonao Nakamura, Takashi Mizowaki
Scientific Reports.2021;[Epub] CrossRef

Thyroid
Validity and Reliability of the Korean Version of the Hyperthyroidism Symptom Scale: Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do Joon Park, Hak Chul Jang, Jae Hoon Moon; Endocrinol Metab. 2018;33(1):70-78. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.70

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Background

Thyrotoxicosis is a common disease resulting from an excess of thyroid hormones, which affects many organ systems. The clinical symptoms and signs are relatively nonspecific and can vary depending on age, sex, comorbidities, and the duration and cause of the disease. Several symptom rating scales have been developed in an attempt to assess these symptoms objectively and have been applied to diagnosis or to evaluation of the response to treatment. The aim of this study was to assess the reliability and validity of the Korean version of the hyperthyroidism symptom scale (K-HSS).

Methods

Twenty-eight thyrotoxic patients and 10 healthy subjects completed the K-HSS at baseline and after follow-up at Seoul National University Bundang Hospital. The correlation between K-HSS scores and thyroid function was analyzed. K-HSS scores were compared between baseline and follow-up in patient and control groups. Cronbach's α coefficient was calculated to demonstrate the internal consistency of K-HSS.

Results

The mean age of the participants was 34.7±9.8 years and 13 (34.2%) were men. K-HSS scores demonstrated a significant positive correlation with serum free thyroxine concentration and decreased significantly with improved thyroid function. K-HSS scores were highest in subclinically thyrotoxic subjects, lower in patients who were euthyroid after treatment, and lowest in the control group at follow-up, but these differences were not significant. Cronbach's α coefficient for the K-HSS was 0.86.

Conclusion

The K-HSS is a reliable and valid instrument for evaluating symptoms of thyrotoxicosis in Korean patients.

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Effect of thyroid-stimulating hormone suppression on quality of life in thyroid lobectomy patients: interim analysis of a multicenter, randomized controlled trial in low- to intermediate-risk thyroid cancer patients (MASTER study)
Ja Kyung Lee, Eu Jeong Ku, Su-jin Kim, Woochul Kim, Jae Won Cho, Kyong Yeun Jung, Hyeong Won Yu, Yea Eun Kang, Mijin Kim, Hee Kyung Kim, Junsun Ryu, June Young Choi
Annals of Surgical Treatment and Research.2024; 106(1): 19. CrossRef
Effect of increased levothyroxine dose on depressive mood in older adults undergoing thyroid hormone replacement therapy
Jae Hoon Moon, Ji Won Han, Tae Jung Oh, Sung Hee Choi, Soo Lim, Ki Woong Kim, Hak Chul Jang
Clinical Endocrinology.2020; 93(2): 196. CrossRef
Clinical Feasibility of Monitoring Resting Heart Rate Using a Wearable Activity Tracker in Patients With Thyrotoxicosis: Prospective Longitudinal Observational Study
Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do Joon Park, Hak Chul Jang, Jae Hoon Moon
JMIR mHealth and uHealth.2018; 6(7): e159. CrossRef

Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1: Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park; Endocrinol Metab. 2015;30(4):584-592. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.584

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Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

Citations

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Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease
Ting-ying Jiao, Yuan-di Ma, Xiao-zhen Guo, Yun-fei Ye, Cen Xie
Acta Pharmacologica Sinica.2022; 43(5): 1103. CrossRef
Loperamide induces excessive accumulation of bile acids in the liver of mice with different diets
Zili Lei, Hedong Rong, Yanhong Yang, Siping Yu, Tianle Zhang, Lei Chen, Ya Nie, Qi Song, Qing Hu, Jiao Guo
Toxicology.2022; 477: 153278. CrossRef
Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Giuseppe Ferrandino, Rachel R. Kaspari, Olga Spadaro, Andrea Reyna-Neyra, Rachel J. Perry, Rebecca Cardone, Richard G. Kibbey, Gerald I. Shulman, Vishwa Deep Dixit, Nancy Carrasco
Proceedings of the National Academy of Sciences.2017;[Epub] CrossRef

Thyroid
The Frequency and Clinical Implications of the BRAF^V600E Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades: A Ram Hong, Jung Ah Lim, Tae Hyuk Kim, Hoon Sung Choi, Won Sang Yoo, Hye Sook Min, Jae Kyung Won, Kyu Eun Lee, Kyeong Cheon Jung, Do Joon Park, Young Joo Park; Endocrinol Metab. 2014;29(4):505-513. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.505

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Background

Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAF^V600E, which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAF^V600E mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed.

Methods

The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAF^V600E mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA.

Results

The prevalence of the BRAF^V600E mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAF^V600E mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAF^V600E mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAF^V600E mutation status.

Conclusion

The BRAF^V600E mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAF^V600E-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAF^V600E mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.

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Genetic and Clinicopathologic Characteristics of Papillary Thyroid Carcinoma in the Chinese Population: High BRAF Mutation Allele Frequency, Multiple Driver Gene Mutations, and RET Fusion May Indicate More Advanced TN Stage
Zhihong Wang, Peng Tang, Surong Hua, Junyi Gao, Bin Zhang, Hua Wan, Qixi Wu, Jiaxin Zhang, Ge Chen
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Lingfeng Tang, Xiujie Shu, Daixing Hu, Chang Deng, Haoyu Ren, Xinliang Su
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Min Jhi Kim, Jin Kyong Kim, Gi Jeong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Woong Youn Chung, Daham Kim, Kee-Hyun Nam
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VE1 immunohistochemistry is an adjunct tool for detection of BRAFV600E mutation: Validation in thyroid cancer patients
Faiza A. Rashid, Sobia Tabassum, Mosin S. Khan, Hifzur R. Ansari, Muhammad Asif, Ahmareen K. Sheikh, Syed Sameer Aga
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Qiang Wang, Ning Zhao, Jun Zhang
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Null Association between BRAF V600E Mutation and Tumor Recurrence in Patients with Papillary Thyroid Microcarcinoma in South Korea
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Young Shin Song, Jung Ah Lim, Hoonsung Choi, Jae‐Kyung Won, Jae Hoon Moon, Sun Wook Cho, Kyu Eun Lee, Young Joo Park, Ka Hee Yi, Do Joon Park, Jeong‐Sun Seo
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Thyroid
The Expression of Tumor-Associated Macrophages in Papillary Thyroid Carcinoma: Seunghwan Kim, Sun Wook Cho, Hye Sook Min, Kang Min Kim, Gye Jeong Yeom, Eun Young Kim, Kyu Eun Lee, Yeo Gyu Yun, Do Joon Park, Young Joo Park; Endocrinol Metab. 2013;28(3):192-198. Published online September 13, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.3.192

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Abstract PDF PubReader

Background

Tumor-associated macrophages (TAMs) play a tumorigenic role related to advanced staging and poor prognosis in many human cancers including thyroid cancers. Yet, a functional role of TAMs in papillary thyroid carcinoma (PTC) has not been established. The aim of this study was to investigate TAM expression in human PTC with lymph node (LN) metastasis.

Methods

Thirty-six patients who underwent surgery after being diagnosed with PTC with LN metastasis were included. Primary tumor tissues were immunohistochemically stained with an anti-CD68 antibody and clinical characteristics according to TAM density were evaluated.

Results

The TAM densities (CD68⁺ cells) varied from 5% to 70%, in all tumor areas, while few cells were stained in adjacent normal tissues. TAMs were identified as CD68⁺ cells with thin, elongated cytoplasmic extensions that formed a canopy structure over tumor cells. Comparing clinicopathologic characteristics between tumors with low (<25%) and high (25% to 70%) TAM densities, primary tumors were larger in the high density group than in the low density group (2.0±0.1 vs. 1.5±0.1; P=0.009).

Conclusion

TAMs were identified in primary PTC tumors with LN metastasis and higher TAM densities were related to larger tumor sizes, suggesting a tumorigenic role of TAMs in human PTCs.

Citations

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Thyroid
Expression of Thyroid Stimulating Hormone Receptor mRNA in Mouse C2C12 Skeletal Muscle Cells: Jung Hun Ohn, Sun Kyoung Han, Do Joon Park, Kyong Soo Park, Young Joo Park; Endocrinol Metab. 2013;28(2):119-124. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.119

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Background

We analyzed whether thyroid stimulating hormone receptor (TSH-R) is expressed in a skeletal muscle cell line and if TSH has influence on the differentiation of muscle cells or on the determination of muscle fiber types.

Methods

TSH-R gene expression was detected with nested real-time polymerase chain reaction (RT-PCR) in C2C12, a mouse skeletal muscle cell line. The effect of TSH on myotube differentiation was assessed by microscopic examination of myotube formation and through the measurement of expression of muscle differentiation markers, i.e., myogenin and myoD, and muscle type-specific genes, i.e., MyHC1, MyHC2a, and MyHC2b, with quantitative RT-PCR before and after incubation of C2C12 myotube with TSH.

Results

TSH-R was expressed in the mouse skeletal muscle cell line. However, treatment with TSH had little effect on the differentiation of muscle cells, although the expression of the muscle differention marker myogenin was significantly increased after TSH treatment. Treatment of TSH did not affect the expression of muscle type-specific genes.

Conclusion

TSH-R is expressed in a mouse skeletal muscle cell line, but the role of TSH receptor signaling in skeletal muscle needs further investigation.

Citations

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Expression and Purification of Phospholipase C-beta4, and Chimeric Phospholipase C and Characterization of Them.: Do Joon Park; Endocrinol Metab. 2012;27(4):282-288. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.282

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Abstract PDF: BACKGROUND
Phospholipase C-beta4 (PLC-beta4) is known to be one of the most important signal transducing molecules; however, its biophysical and chemical characteristics are not well known due to the difficulty in purifying PLC-beta4 from bovine retina. In the present study, we used the baculovirus expression system in order to express and purify large amounts of PLC-beta4. With this system, we also tried to produce chimeric PLC-beta3/beta4 and PLC-beta4/beta3 protein in order to study the structure-activity relationship between N terminal and C terminal portion of PLC-betas. METHODS: I cloned PLC-beta4 to the baculovirus expression system by the polymerase chain reaction method and infected the PLC-beta4 to Sf9 cells. I purified recombinant PLC-beta4 proteins using sequential high performnance liquid chromatography (HPLC) by using the TSK phenyl-5PW column and the TSK heparin-5PW column. With this similar method, I was able to express chimeric PLC-beta3/beta4 and PLC-beta4/beta3 proteins. RESULTS: With the two step HPLC, I was able to purify PLC-beta4 by 30-fold; this purified PLC-beta4 contained PLC activity. I also expressed chimeric PLC-beta3/beta4 and PLC-beta4/beta3 using the baculovirus system, and their expression was confirmed by the immunoblot method. However, chimeric PLC-beta4/beta3 did not show PLC activity, while chimeric PLC-beta3/beta4 retained its PLC-activity. CONCLUSION: Expression of chimeric PLC-beta4 using the baculovirus system was an efficient method to obtain a large amount of protein. Moreover, this expression and purification method would be useful in studying the physical and chemical characteristics of this protein. In my study using chimeric PLC-beta protein by swapping the N terminal and C terminal portions of PLC-beta3 and beta4, chimeric protein lost its activity completely in PLC-beta4/beta3 chimera. This result suggested a minute change in the tertiary structure of the protein, which may significantly affect its function.

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